EFFECT OF 3 DIFFERENT MODES OF ALCOHOL ADMINISTRATION ON THE ACTIVITYOF THE RAT HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

The present study compared the effect of different modes of alcohol ad ministration on the activity of the hypothalamic-pituitary-adrenal (HP A) axis, In a first series of studies, we investigated the influence o f the intraperitoneal (ip) and intragastric (ig) effect of acutely adm inistered alcohol, Over a 3-hr period, alcohol induced dose-related in creases in adrenocorticotropic hormone (ACTH) and alcohol levels in th e circulation. There was a good correlation between blood ACTH and alc ohol levels tip treatment, R = 0.84; ig treatment, R = 0.79), Measurem ent of steady-state mRNA of the immediate early gene NGFI-B, taken as an index of neuronal activation in the paraventricular nucleus (PVN) o f the hypothalamus of rats administered 3 g of alcohol/kg, indicated s ignificant (p < 0.01) increases between 60 and 180 min after both ip a nd ig alcohol injection, with peak stimulation at 1 and 2 hr, respecti vely. Although NGFI-B mRNA levels had returned to control level in the parvicellular portion of the PVN of animals administered the drug ip 4 hr earlier, they were still significantly (p < 0.01) elevated 4 hr a fter ig treatment, A second series of studies used rats fed an alcohol diet containing 6.4% alcohol (w/v), or pair-fed, The rats were tested during the 4th or 6th night of treatment, Despite blood alcohol level s ranging between 0.060 and 0.140% w/v, there was no significant rise in plasma ACTH/corticosterone levels in animals fed the drug, and no d etectable NGFI-B mRNA in their PVN, Collectively, these results indica te that both the ip and the ig acute injection of alcohol induced dose -related increases in plasma ACTH levels, PVN neuronal activation was also observed, In contrast, the alcohol diet had no effect on HPA horm one levels or PVN expression of NGFI-B.